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Combinatorial transcription factor profiles predict mature and functional human islet α and β cells. | LitMetric

AI Article Synopsis

  • * This study analyzed over 40,000 human islet cells through single-cell RNA sequencing to uncover the diversity in TF expression among these cells.
  • * It was found that specific combinations of TFs (ARX/MAFB in α cells and MAFA/MAFB in β cells) lead to enhanced gene expression related to glucose sensing and hormone secretion, indicating these combinations mark more functional and mature cell subpopulations.

Article Abstract

Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells, and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression. Subpopulations of islet cells coexpressing ARX/MAFB (α cells) and MAFA/MAFB (β cells) exhibited greater expression of key genes related to glucose sensing and hormone secretion relative to subpopulations expressing only one or neither TF. Moreover, all subpopulations were identified in native pancreatic tissue from multiple donors. By Patch-Seq, MAFA/MAFB-coexpressing β cells showed enhanced electrophysiological activity. Thus, these results indicate that combinatorial TF expression in islet α and β cells predicts highly functional, mature subpopulations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492318PMC
http://dx.doi.org/10.1172/jci.insight.151621DOI Listing

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